G S Howarth1, C J Xian, L C Read. 1. Cooperative Research Centre for Tissue Growth and Repair, and Child Health Research Institute, North Adelaide, South Australia, Australia. ghowarth@medicine.adelaide.edu.au
Abstract
BACKGROUND: Insulin-like growth factor-I (IGF-I) is currently under evaluation for the treatment of a variety of chronic disease conditions. We investigated the safety of long-term IGF-I administration in a rat model of inflammatory bowel disease which predisposes to the development of dysplasia. METHODS: Chronic consumption of dextran sulphate sodium (DSS) by rats manifests a colitis with dysplastic features. Rats consumed 2% DSS for 4 weeks when pumps were implanted to deliver either vehicle or IGF-I for 15 or 20 weeks while rats continued to consume DSS. Features of colitis and dysplasia were assessed at kill. RESULTS: Compared to vehicle, 20 weeks IGF-I significantly increased body weight by 19% and total gut weight by 43%. Colonic crypt depth, proliferative compartment, labelling index, dysplasia, neoplasia and other indices of colitis were not significantly affected. CONCLUSIONS: Twenty weeks administration of IGF-I to rats induced growth of the intestine but did not affect the severity of experimentally-induced colitis or the incidence or progression of colonic dysplasia.
BACKGROUND:Insulin-like growth factor-I (IGF-I) is currently under evaluation for the treatment of a variety of chronic disease conditions. We investigated the safety of long-term IGF-I administration in a rat model of inflammatory bowel disease which predisposes to the development of dysplasia. METHODS: Chronic consumption of dextran sulphate sodium (DSS) by rats manifests a colitis with dysplastic features. Rats consumed 2% DSS for 4 weeks when pumps were implanted to deliver either vehicle or IGF-I for 15 or 20 weeks while rats continued to consume DSS. Features of colitis and dysplasia were assessed at kill. RESULTS: Compared to vehicle, 20 weeks IGF-I significantly increased body weight by 19% and total gut weight by 43%. Colonic crypt depth, proliferative compartment, labelling index, dysplasia, neoplasia and other indices of colitis were not significantly affected. CONCLUSIONS: Twenty weeks administration of IGF-I to rats induced growth of the intestine but did not affect the severity of experimentally-induced colitis or the incidence or progression of colonic dysplasia.
Authors: Suzanne M Abimosleh; Ruth J Lindsay; Ross N Butler; Adrian G Cummins; Gordon S Howarth Journal: Dig Dis Sci Date: 2011-12-07 Impact factor: 3.199
Authors: Chloe J Mitchell; Gordon S Howarth; Lauren C Chartier; Debbie Trinder; Ian C Lawrance; Li San Huang; Suzanne Mashtoub Journal: Exp Biol Med (Maywood) Date: 2020-09-09
Authors: Haydn L Atkins; Mark S Geier; Luca D Prisciandaro; Ashok K Pattanaik; Rebecca E A Forder; Mark S Turner; Gordon S Howarth Journal: Dig Dis Sci Date: 2011-10-26 Impact factor: 3.199